Novel protein biomarker for breast and lung cancer

Professor El-Tanani is leading research into novel targeted therapeutics (Ran-inhibitors) for the treatment of triple negative breast cancer and to reverse chemotherapy resistance in lung cancer.

Translational research led by Prof Mohamed El-Tanani at the Institute of Cancer Therapeutics is focused on a novel protein biomarker for breast and lung cancer called Ran GTPAse (Ran). Ran is overexpressed in a range of tumors and is associated with local invasion, metastasis and reduced patient survival. The team have shown that reducing levels of Ran leads to cytotoxicity in a range of cancer cells and that a high level of Ran in patients with breast cancer is predictive for the development of metastasis and can lead to resistance to current drugs for breast and lung cancer.

The research has two objectives; the first is to identify and develop molecules (drug candidates) that have the ability to reduce the levels of Ran in cancer cells, the second is to develop a simple test (Ran DX) using blood samples to determine levels of Ran in breast and lung cancer patients.

Millions of compounds with the potential to inhibit Ran have been screened to find the most potent, and the team now have two very strong candidates ready to move forward into clinical trials. One candidate is a 'repurposed' drug that has been pre-clinically validated in breast and lung cancer. The second is a novel peptide which has been tested successfully in preclinical models. In addition, the researchers are working on the development of a monoclonal antibody for Ran (Ran-mAb) which has the potential to be a potent Ran inhibitor. The team at Bradford has attracted interest from the pharmaceutical industry and investors and is currently seeking financial backing to progress the best candidates into clinical trials.

The annual incidence of breast cancer in the UK is 50,000 and around 1,000 die every month. 5 in every 100 patients have metastasis when first diagnosed, and a further 35 will develop metastasis within 10 years, representing considerable disease burden. The challenge is predicting metastatic disease early enough to improve patient outcomes. In collaboration with a UK based SME, Imhotep Diagnostics and Therapeutics (IDT Ltd), the Bradford team has recently won an Innovate UK grant to fund the development of a novel blood test for Ran. This test will enable breast cancer metastatic risk to be predicted at the time of diagnosis and allow patient stratification that will ensure optimum treatment is made available including choice of chemotherapy and follow-up patient prognosis.

The project will start in May 2018 and it is hoped over the next few years the research will translate into an important predictive test for the monitoring of breast cancer patients.